Association of Gene Polymorphisms in APOE and BIN1 With Dementia of Alzheimer's Type Susceptibility in Chinese Han Population

Objectives: Dementia of the Alzheimer's type (DAT) is the most common chronic neurodegenerative disease. At present, the pathogenesis of DAT is not completely clear, and there are no drugs that can cure the disease. Once an individual is diagnosed with DAT, the survival time is only 3 to 9 years. Therefore, there is an urgent need to determine the etiology of DAT and the associated influencing factors to find a breakthrough in the treatment of DAT.Methods: We studied the relationship between polymorphisms in several genes (including BIN1 and APOE) and DAT susceptibility and the effects of sex differences on DAT. Our study included 137 patients with DAT and 509 healthy controls (HCs).Results: The APOE rs429358 polymorphism CC and CT genotypes were associated with an increased risk of DAT in women. We found a significant association between APOE ε4 and DAT. The frequency of the ε4 allele in the DAT group (15.5%) was higher than that in the HC group (8.7%). The BIN1 rs7561528 polymorphism was associated with a decreased risk of DAT in men.Conclusions: APOE gene rs429358 and BIN1 gene 7561528 genes may affect the susceptibility to DAT in a Chinese Han population.

Blinded Clinical Evaluation for Dementia of Alzheimer’s Type Classification Using FDG-PET: A Comparison Between Feature-Engineered and Non-Feature-Engineered Machine Learning Methods

Background: Advanced machine learning methods can aid in the identification of dementia risk using neuroimaging-derived features including FDG-PET. However, to enable the translation of these methods and test their usefulness in clinical practice, it is crucial to conduct independent validation on real clinical samples, which has yet to be properly delineated in the current literature. Objective: In this paper, we present our efforts to enable such clinical translational through the evaluation and comparison of two machine-learning methods for discrimination between dementia of Alzheimer’s type (DAT) and Non-DAT controls. Methods: FDG-PET-based dementia scores were generated on an independent clinical sample whose clinical diagnosis was blinded to the algorithm designers. A feature-engineered approach (multi-kernel probability classifier) and a non-feature-engineered approach (3D convolutional neural network) were analyzed. Both classifiers were pre-trained on cognitively normal subjects as well as subjects with DAT. These two methods provided a probabilistic dementia score for this previously unseen clinical data. Performance of the algorithms were compared against ground-truth dementia rating assessed by experienced nuclear physicians. Results: Blinded clinical evaluation on both classifiers showed good separation between the cognitively normal subjects and the patients diagnosed with DAT. The non-feature-engineered dementia score showed higher sensitivity among subjects whose diagnosis was in agreement between the machine-learning models, while the feature-engineered approach showed higher specificity in non-consensus cases. Conclusion: In this study, we demonstrated blinded evaluation using data from an independent clinical sample for assessing the performance in DAT classification models in a clinical setting. Our results showed good generalizability for two machine-learning approaches, marking an important step for the translation of pre-trained machine-learning models into clinical practice.

Pharmacological investigations on efficacy of Phlorizin a sodium-glucose co-transporter (SGLT) inhibitor in mouse model of intracerebroventricular streptozotocin induced dementia of AD type

Objectives The study has been commenced to discover the potential of Phlorizin (dual SGLT inhibitor) in streptozotocin induced dementia of Alzheimer’s disease (AD) type. Material and methods Injection of Streptozotocin (STZ) was given via i.c.v. route (3 mg/kg) to induce dementia of Alzheimer’s type. In these animals learning and memory was evaluated using Morris water maze (MWM) test. Glutathione (GSH) and thiobarbituric acid reactive species (TBARS) level was quantified to evaluate the oxidative stress; cholinergic activity of brain was estimated in term of acetylcholinesterase (AChE) activity; and the levels of myeloperoxidase (MPO) were measured as inflammation marker. Results The mice model had decreased performance in MWM, representing impairment of cognitive functions. Biochemical evaluation showed rise in TBARS level, MPO and AChE activity, and fall in GSH level. The histopathological study revealed severe infiltration of neutrophils. In the study, Phlorizin/Donepezil (serving as positive control) treatment mitigate streptozotocin induced cognitive decline, histopathological changes and biochemical alterations. Conclusions The results suggest that Phlorizin decreased cognitive function via its anticholinesterase, antioxidative, antiinflammatory effects and probably through SGLT inhibitory action. It can be conferred that SGLTs can be an encouraging target for the treatment of dementia of AD.

Aspirin in people with dementia, long-term benefits, and harms: a systematic review

Purpose People with dementia may have indications for aspirin prescription and clinicians are asked to balance the potential risks against benefits. This review examines the evidence for the risk and benefit of long-term aspirin use in people with dementia aged over 65 years, including randomised controlled trials and observational studies. Methods We searched three databases for research published between 2007 and 2020. Each eligible article was assessed for risk of bias, and confidence in findings was rated using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results Four papers met inclusion criteria: one randomised controlled trial, two cohort studies, and one with pooled data. All looked only at dementia of Alzheimer’s type, and none addressed myocardial or cerebral infarction as outcomes. Dementia progression was reported by two studies, with conflicting results. The trial found no significant effect of aspirin on mortality (odds ratio aspirin vs. no aspirin 1.07, 95% confidence interval 0.58–1.97) but found more events of severe bleeding with aspirin (OR aspirin vs. no aspirin 6.9, 1.5–31.2). An excess in intracranial haemorrhage in the aspirin group was judged plausible based on two non-randomised studies. Conclusions The review findings are limited because studies include only people with Alzheimer’s-type dementia and lack confirmatory studies, although an increased risk of bleeding events is recognised. Further research that addresses the benefits and risks of aspirin in more representative groups of people with dementia is needed to guide prescribing decisions.

Assessment of Cognitive-Communicative Functions in Persons With Mild Cognitive Impairment and Dementia of Alzheimer's Type

According to world population prospects data report, older individuals, especially those aged 60 years and above, have increased substantially over the recent year, which is going to accelerate in the coming decades. The most common problems the aging population faces are dementia of the Alzheimer's type (DAT) and mild cognitive impairment (MCI). Assessment of cognitive-communicative markers is essential for persons with MCI and DAT. Furthermore, it can help in the differential diagnosis of DAT and MCI. Proper assessment by speech-language pathologists is warranted in this area as it will throw light on the differential diagnosis of MCI and DAT, the clinical description of the characteristics between the two clinical groups, the prognosis for improved outcomes, recommendations for intervention and support, and referral for other professionals for assessments or services.